Protection from Cryptosporidium parvumInfection by γδ T Cells in Mice that Lack αβ T Cells

Background and Purpose: Cryptosporidium parvum establishes a parasitic relationship with epithelial cells of the intestine. Infection with this protozoan is resolved in the immunocompetent host, but persistent life-threatening infection develops in the immunocompromised host. We propose that γδ T Cells in the intestinal mucosa play a role in immunity to C. parvum. Methods: Intestinal intra-epithelial lymphocyte and lamina propria T-cell subsets were examined in mice infected with C.parvum. The mice are homozygous for a deletion of the TCR chain gene, TCR (-/-) and, therefore, lack conventional γδ T Cells, but retain a population of γδ T Cells with T-cell receptors. To examine the contribution of γδ T Cells to immunity, these mice were treated with monoclonal antibody GL3-3A, specific for this T-cell receptor, then were inoculated with C.parvum oocysts. Lymphocyte subsets and hematoxylin and eosin (H&E)-stained intestinal sections from untreated mice were compared with those from mice treated with either a low dose of GL3-3A for 6 weeks, or a high dose of GL3-3A for 16 weeks. Results: The proportion of γδ T Cells in the lamina propria increased in infected mice. In mice treated with a low dose of GL3-3A, a population of γδ T Cells that had characteristics of activated cells, was still evident 6 weeks after inoculation. No C.parvum developmental forms were identified in the intestinal sections of mice under these conditions. However, TCR (-/-) mice treated with a high dose of GL3-3A were depleted of γδ T Cells, and 50% of the mice were infected with C.parvum. Conclusions: The γδ T Cells contribute to protection against C.parvum infection. In the absence of conventional γδ T Cells, activation of intestinal γδ T Cells may prevent infection with this organism.